We have now completed three years of a four-year cycle. The primary aim of the new program direction team of the GCRC during this time was to address shortcomings identified in previous reviews and to continue to build our program for the future. We have completed the renovation of our inpatient unit and now have a state-of-the-art facility to conduct clinical research. We have relocated our Core Laboratory to new, updated and convenient space near the inpatient unit. We have improved our productivity in all spheres of activity, with steady growth in number of A days and visits, number of protocols, number and diversity of investigators, increased number of medical students and post-doctoral trainees on the unit and expansion of the scope of training activities. This has been accompanied by a substantial increase in publication productivity by GCRC investigators. Our new Research Subject Advocate (RSA) program has played an important role in assisting and educating GCRC investigators in the areas of research subject consent, safety monitoring and regualtory compliance. The Core Laboratory expanded its services in genomics and other DNA technologies, and our new Exercise Physiology and Body Composition Laboratory has been providing services to a growing number of investigators. The level of activiy and excitement on the GCRC has never been higher. In this competing renewal proposal, 66 different principal investigators will perform 89 protocols in several areas including genetic epidemiology of connective tissue diseases and other disorders, pharmacogenetics, dementia research, gene expression profiling in cancer, HIV natural history and pathogenesis, exercise physiology in chronic diseases, and metabolic research with an emphasis on pathogenesis and treatment obesity, hypertension, bone loss and diabetes mellitus. These complement several other already active programs including oncology and psychopharmacology of drug addiction. These areas cover many of the emerging critical health issues as the population ages. Our focus over the next 5 years will be to continue to expand training on the GCRC; continue to expand our protocol diversity; and invest in and expand new laboratory and informatics technologies to allow the GCRC investigators to meet the research challenges of the future. To this end, we are requesting new resources to expand our services in database design, genomics capabilities and exercise physiology. As we do so, we will continue to perform this research with the highest standards of patient care, ethics, safety and regulatory compliance.